Although much information on the sites and mechanisms of plasma protein biosynthesis is available, very little is known about the sites or regulation of catabolism of these circulating proteins. We have designed a non-biodegradable radioactive tag, 3H-raffinose, which permits, for the first time, identification of the sites of uptake and degradation of plasma proteins with long circulation half-lives. Using the raffinose label we will determine the tissue sites of catabolism of albumin, IgG and IgM, 3 major plasma proteins whose turnover appears to be regulated independently. In addition, we have already demonstrated that the carbohydrate on the immunoglobulins can target immune complexes to specific tissues for clearance and degradation. We will evaluate, therefore, the extent to which carbohydrate can also influence the normal turnover of these glycoproteins. We are also using the raffinose label to evaluate the sites and mechanisms of beta-glucocerebrosidase catabolism after intravenous administration to rats. These studies provide a model for understanding, and potentially for manipulating, the in vivo fate of this enzyme which is used in clinical trials of enzyme replacement therapy for Gaucher's disease, a lysosomal storage disorder.